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CME / ABIM MOC

HER2-Mutated Metastatic Non-Small Cell Lung Cancer: Key Pearls for Your Practice 

  • Authors: Fred Hirsch, MD, PhD; Enriqueta Felip, MD, PhD; Stephen Liu, MD
  • CME / ABIM MOC Released: 10/14/2022
  • Valid for credit through: 10/14/2023
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  • Credits Available

    Physicians - maximum of 0.50 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.50 ABIM MOC points

    You Are Eligible For

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Target Audience and Goal Statement

This activity is intended for oncologists, pulmonologists, pathologists, and other members of the multidisciplinary care team involved in the care of patients with HER2-mutated metastatic NSCLC.

The goal of this activity is that learners will be better able to understand HER2-mutated metastatic NSCLC and how to optimize the care of these patients as part of the multidisciplinary team. 

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Clinical trial data evaluating therapies for patients with HER2-mutated metastatic NSCLC
  • Have greater competence related to
    • Identifying HER2 mutations in patients with metastatic NSCLC
    • Personalizing care for patients with HER2-mutated metastatic NSCLC
    • Managing adverse events in patients receiving therapy for HER2-mutated metastatic NSCLC


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Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.

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Faculty

  • Fred Hirsch, MD, PhD

    Professor of Medicine
    Icahn School of Medicine
    Mount Sinai Hospital
    Director
    Center of Excellence for Thoracic Oncology
    Tisch Cancer Institute
    New York, New York, United States

    Disclosures

    Fred Hirsch, MD, PhD, has no relevant financial relationships.

  • Enriqueta Felip, MD, PhD

    Head of Thoracic Oncology Unit
    Vall d'Hebron University Hospital
    Barcelona, Spain

    Disclosures

    Enriqueta Felip, MD, PhD, has the following relevant financial relationships:
    Consultant or advisor for: AbbVie; Amgen; AstraZeneca; Bayer; Bristol-Myers Squibb; Daiichi Sankyo; Eli Lilly; F. Hoffmann-La Roche; GlaxoSmithKline; Janssen; Merck; Merck Sharp & Dohme; Novartis; Peptomyc; Pfizer; Sanofi; Takeda
    Speaker or member of speakers bureau for: AstraZeneca; Bristol-Myers Squibb; Eli Lilly; F. Hoffmann-La Roche; Janssen; Merck; Merck Sharp & Dohme; Pfizer; Sanofi; Takeda; TouchOncology
    Research funding from: Merck Healthcare

  • Stephen Liu, MD

    Associate Professor of Medicine
    Georgetown University
    Director of Thoracic Oncology and Developmental Therapeutics
    Georgetown Lombardi Comprehensive Cancer Center
    Washington, DC, United States

    Disclosures

    Stephen Liu, MD, has the following relevant financial relationships:
    Consultant or advisor for: Amgen; AstraZeneca; Bayer; BeiGene; Blueprint; Boehringer-Ingelheim; Bristol-Myers Squibb; Catalyst; Daiichi Sankyo; Eisai; Elevation Oncology; Genentech/Roche; Gilead; Guardant Health; Janssen; Jazz Pharmaceuticals; Lilly; Merck/MSD; Novartis; Regeneron; Sanofi; Takeda; Turning Point Therapeutics
    Research funding from: Alkermes; Bayer; Blueprint; Bristol-Myers Squibb; Elevation Oncology; Genentech; Gilead; Merck; Merus; Nuvalent; Pfizer; RAPT; Turning Point Therapeutics

Editor

  • Lisa Cockrell, PhD

    Medical Education Director, Medscape, LLC

    Disclosures

    Lisa Cockrell, PhD, has no relevant financial relationships.

Compliance Reviewer

  • Lisa Simani, APRN, MS, ACNP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Lisa Simani, APRN, MS, ACNP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC

HER2-Mutated Metastatic Non-Small Cell Lung Cancer: Key Pearls for Your Practice 

Authors: Fred Hirsch, MD, PhD; Enriqueta Felip, MD, PhD; Stephen Liu, MDFaculty and Disclosures

CME / ABIM MOC Released: 10/14/2022

Valid for credit through: 10/14/2023

processing....

Activity Transcript

Chapter 1

Fred Hirsch, MD, PhD: Hello everyone. My name is Dr Fred Hirsch. I am a Professor of Medicine and Pathology at Icahn School of Medicine at Mount Sinai Hospital in New York and the Executive Director for the Center of Excellence for Thoracic Oncology. Today, I would like to talk with you briefly about molecular testing for HER2 in non-small cell lung cancer (NSCLC).

We have several HER2 alterations to deal with. We have mutations, we have amplifications, and we have overexpression, and the prevalence of the different abnormalities may vary. They are not very frequent, but they are there, and taking the total number of patients into account, each of them represents a substantial part of the lung cancer population, even if the prevalence and the frequency percentages are small. We do not know exactly the overlap, the Venn diagram, but there is some overlap though it might not be that much between these 3 abnormalities.

HER2 mutation is mutually exclusive from other driving mutations. There seems to be some intratumoralertuzumabl heterogeneity in lung adenocarcinomas. We see it most frequently in females, never smokers, and in adenocarcinoma or adenosquamous histology. It has an adverse outcome compared to other driving mutations, which might be because of lack of effective HER2-targeted strategies until very recently. Last, but not least, there is unfortunately a tendency for brain metastasis in this particular subgroup of patients.

There are recommendations for sample collection, processing, and storage. Tumor tissue, cytology specimens, and circulating tumor (ctDNA) can all be used for HER2 testing. However, tumor tissue is preferred. We know that there might be false-negative findings with ctDNA, but we are often limited by tumor tissue availability. So if we do not have tissue availability, we should go to liquid biopsy and ctDNA. Next-generation sequencing (NGS) is the preferable and suitable assessment for HER2 mutation. NGS can identify all types of variations in HER2 related to clinical treatment, including exon 20 insertions, amplifications, and copy number variations. Currently, HER2 amplification and overexpression is not requested for drug treatment targeting HER2, but as I will touch upon later, it might be relevant.

Antibody-drug conjugates are a new development in the drug development for cancer therapy. It contains an antibody conjugated to a cytotoxic drug payload. It widens the therapeutic window. My point here is, we are dealing with monoclonal antibodies, and when we are talking about antibodies, mutation might not be the best biomarker. We do not know at this stage, but immunohistochemistry (IHC) might be more relevant when we are talking about antibody-drug conjugates in the future.

The National Comprehensive Cancer Network (NCCN) guidelines recommend broad molecular testing. HER2 mutation should be included in that testing panel and we need to ensure that the patients can receive the most appropriate treatment and be eligible for further clinical trials. I would like to mention, though, that we have work to do in terms of molecular testing for patients with NSCLC. An eye-opener was a presentation a year ago from US Oncology Network Study, showing that < 50% of patients had all 5 biomarkers tested. That is a very low percentage. Of course, if you're looking at a single mutation, EGFR testing is more frequent, but we need to be sure that patients get a broader panel of gene analysis using NGS. So, we have educational work to do together.

That was a brief overview of testing for HER2 mutations. I thank you for participation in this activity and there will be questions later on.

Chapter 2

Enriqueta Felip, MD, PhD: Hello, my name Enriqueta Felip, and I'm from Vall d'Hebron University Hospital in Barcelona, Spain. In this section, I would like to summarize some of the data supporting the use of HER2-targeted agents in metastatic NSCLC. Early studies with trastuzumab showed no real benefit in patients with HER2 mutations or HER2 overexpression. Attention then turned to antibody drug conjugates, and I would like to highlight trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd).

An initial study analyzed T-DM1 in 18 patients with HER2 mutations and NSCLC. In this group of 18 patients, the response rate was 44% with T-DM1 with a median duration of response of 4 months and a median progression-free survival of 5 months.

Then we have T-DXd and this has been analyzed in two phase 2 trials, DESTINY-Lung01 and the DESTINY-Lung02, which led to recent approval of T-DXd by the FDA.

I would like to first summarize the DESTINY-Lung01 study. In this trial, 85 patients with HER2 mutations heavily pretreated with standard therapy, received T-DXd and the response rate was 54.9% and a median duration of response 9.3 months. There were patients previously treated even with a tyrosine kinase inhibitor (TKI) and also patients without HER2 overexpression had response. Progression-free survival was 8.2 months in this trial and median overall survival was 17.8 months.

The DESTINY-Lung02 trial compared 2 different doses of T-DXd. With the dose of 5.4mg/kg of T-DXd, the response rate was 57.7% and the median duration of response was 8.7 months. This was also a group of previously treated patients.

There are other agents with results in the area of HER2 mutations. Poziotinib is an irreversible pan-HER2 inhibitor. There was initial cohort of 30 patients with a 27% response rate and a medium progression-free survival of 5.5 months and also in a larger cohort of patients, 90 patients, the results were similar with a median progression-free survival of 5.5 months. And then there was a French trial published in the Journal of Clinical Oncology analyzing the combination of trastuzumab, pertuzumab, and docetaxel in this group of patients with HER2 mutations and the median progression-free survival was approximately 6 months.

So T-DXd is a very active agent in patients previously treated with HER2 mutations. I would like to highlight 2 trials analyzing this compound in the first line. DESTINY-Lung03 is a phase 1b trial analyzing T-DXd plus durvalumab plus platinum-pemetrexed in the first line treatment of patients with HER2 positive tumors. And also in the DESTINY-Lung04 trial, patients with HER2 mutations and who are treatment-naive are randomized to receive T-DXd or the combination of platinum-pemetrexed plus pembrolizumab. These trials will help us to know exactly the place of targeted agents in the first line setting of patients with HER2 mutations.

Thank you for participating in this activity and please go on to answer the question that follows.

Chapter 3

Stephen Liu, MD: Hello. My name is Dr. Stephen Liu, and I’m a medical oncologist from Georgetown University in Washington, DC. I'm here with Dr Enriqueta Felipe from Vall d'Hebron Hospital in Barcelona, Spain. In this section, we will discuss some considerations when tailoring HER2 targeted therapy based on disease- and patient-related characteristics.

Enriqueta, what challenges do you face when you are thinking about HER2 testing in patients with metastatic non-small-cell lung cancer?

Dr Felip: We still have challenges to have access to NGS technologies. It is recommended by ESMO guidelines for NGS analysis in all patients with nonsquamous histology and stage four disease. There are a number of tests recommended at Level I, so we need to know the results of EGFR mutations, ALK1, ROS1, MET amplification, etc. And also now HER2 mutations. Thus NGS is a standard. We are increasing the percentage of patients with NGS analysis, but it is important to have a look on that and to ensure the NGS determination for all patients, not only in the tumor tissue, but also in liquid biopsy.

Dr Liu: And I think one thing that is unique about HER2 is that this is a gene we know about in oncology, but in a different context. And there are some slightly different variables that we need to consider with HER2. HER2 is very well known not only in breast cancer, and also other cancers like stomach cancer. In the setting of breast cancer, we are talking about HER2 gene amplification and over expression, while for non-small cell lung cancer it really is the DNA mutation. These are very different biomarkers for the same gene, and different tests are used to reveal those biomarkers. It does take some general understanding of precisely what we are looking for and what test to order. Interpreting the test results is of paramount importance. Now, once a HER2 mutation is identified in your patient with advanced non-small cell lung cancer, how do you go about treating that patient?

Dr Felip: At present, we do not have any targeted agent approved in the first line setting of patients with HER2 mutations. I think it is important to know if the patient has or does not have this mutation. We discuss with the patient chemotherapy versus chemotherapy plus immunotherapy. It is true that in my opinion, the role of immunotherapy in these patients is limited, but it is also true that, for example, in the clinical trials these patients were not excluded. In general, we discuss these two possibilities with the patient, chemotherapy versus chemotherapy plus immunotherapy. It is true that we need new treatment options in the first line setting for these patients. I think it is important to analyze the role of targeted agents also in the first line. I would like to highlight the study in patients with HER2 mutations comparing first-line trastuzumab deruxtecan versus standard of care chemotherapy plus immunotherapy. This could help us to identify a new treatment approach for the first line setting in this group of patients.

Dr Liu: It is interesting to think about immunotherapy and while it has changed our treatment of non-small cell lung cancer, it seems that most of the benefit is carried by our smoking population and not so much in the driver-positive patients. What do you think is the role for immune checkpoint inhibitors in patients with HER2-mutated lung cancer going forward? If it is not first line, is it second line? Is it third line or beyond? Is there any role at all?

Dr Felip: We just do not know for sure. We know that in the first line trials, these patients with HER2 mutations were probably included in the trial. It is true that this represents only 1.5% or 2% of all patients. I think if there is a role probably it is in the first line for this. I would agree with the design of the phase 3 trial in first line, comparing trastuzumab deruxtecan versus chemotherapy plus immunotherapy. I think immunotherapy as monotherapy in second or third line has no role.

Dr Liu: Yes, very unimpressed by those data. We know now there are two HER2-targeted agents that are recommended by the NCCN for the management of HER2-mutated non small cell lung cancer, trastuzumab emtansine and trastuzumab deruxtecan. One of these, trastuzumab deruxtecan is now FDA-approved with the accelerated approval based on DESTINY-Lung02. Enriqueta, what factors do you consider when thinking about these two options for patients with HER2-mutated non small cell lung cancer?

Dr Felip: I think these two ADCs are active. I am really impressed with the results of trastuzumab deruxtecan in patients previously treated with HER2 mutations. We have two phase 2 trials with very promising results, showing more than a 50% response rate, with a median duration of response longer than 8 months and median PFS of 9 months. I think my first choice for these patients would be trastuzumab deruxtecan.

Dr Liu: I agree. Well, thank you Enriqueta for joining me, and thank you for participating in this activity. Please go on to answer the question that follows.

Chapter 4

Dr Liu: My name is Dr Stephen Liu, and I'm a medical oncologist from Georgetown University in Washington, DC. Here, I will discuss how to identify and manage some of the potential toxicities that can occur with HER2-targeted agents.

When we think of T-DM1 in the phase 2 trial, this drug was well tolerated, and overall toxicities were primarily grade 1 and 2. I will call attention to infusion reactions. These were characterized by mild rigors, chills, pruritis, and wheezing during treatment, and they did occur in over a quarter of patients. But all of these resolved by simply slowing down the infusion of the T-DM1 and administering antihistamines. This did not preclude retreatment.

We move forward to the approved antibody drug conjugate for HER2-mutated NSCLC, T-DXd. These toxicities were primarily grade 1 and 2, and looking at the DESTINY-Lung01 study, the most common grade 3 treatment-related adverse events were neutropenia and anemia.

These are largely paper toxicities, hopefully without much clinical consequence, but other common events that your patients can notice will include gastrointestinal (GI) toxicities such as nausea, diarrhea, and constipation, as well as fatigue, loss of appetite, alopecia to some degree, and other hematologic events. Again, primarily neutropenia and anemia, but some degree of leukopenia as well.

About 25% of patients in DESTINY-Lung01 discontinued treatment because of drug-induced related adverse events. Our biggest concern initially was with interstitial lung disease (ILD). If we look at the adjudicated drug-related ILD, we do see that about 26% of patients in DESTINY-Lung01 did experience some ILD. There were unfortunately 2 fatal cases. Most of the cases, however, were grade 1 and grade 2. We do know that ILD can occur with T-DXd. Is this related to prior smoking? Unknown, but we do know this is not predictable. It is idiosyncratic and all of our patients do need to be carefully monitored. When patients present with pneumonitis, it is very important we promptly initiate corticosteroids.

If we look at the DESTINY-Lung02 data, this was a randomized trial that compared 2 different doses of T-DXd for HER2-mutated, previously treated NSCLC: the 6.4 mg/kg dose used in DESTINY-Lung01 and the 5.4 mg/kg dose approved in other tumors. At this lower dose, we did see a slightly higher response rate, but importantly, we saw a much lower incidence of pneumonitis, lower grade pneumonitis, and fortunately, this was much more easily identified now down into the single digits.

Pneumonitis remains a concern and primarily it is one not meant to discourage use, but one to encourage awareness of for both the patient and providers. Early recognition of ILD can help early intervention and prevent complications or escalation of toxicity. Overall, these are very safe agents and should be used cautiously in certain cases. Thank you for participating in this activity. Please go on to answer the question that follows.

Chapter 5

Dr Felip: Hello. My name is Enriqueta Felipe, I am from Barcelona, Spain, and I'm here today with Dr Stephen Liu from Georgetown University in Washington, DC. In this section, we will discuss effective communication strategies with patients who have HER2-mutated metastatic NSCLC, including addressing some of their concerns.

Stephen, I would like to discuss with you communication strategies in 2 different scenarios -- testing, and then discussing treatment options. Perhaps, let us first discuss testing. How do you describe molecular testing to your patients with metastatic NSCLC? What questions do they have?

Dr Liu: Well, I think that when I discuss testing with patients, which I think is very important, I think it is very important to outline exactly why we're doing this testing and what that testing is. Generally, I tell patients that cancer, especially lung cancer, is a genetic disease. That does not necessarily mean something we inherit or pass on, but really is the result of changes in the genetic material in our lungs. We all come from different backgrounds and have different levels of understanding of this type of science, and so I make sure that the space is open and we are free to ask questions and explain things in different ways. Really, we are looking for, what is the hidden vulnerability in this specific cancer? What is the most rational, the most intelligent way to target it, to take advantage of its specific weaknesses? If we can learn more about the cancer, we are better equipped to treat it.

When we think of different cancers, I think it is very clear that we treat breast cancer and brain cancer and lung cancer very differently. I try to explain that within lung cancer, there are equal differences there that are important to leverage. And it's these differences that we need to identify to guide therapy from the very beginning. They often ask questions about, what does the testing involve? I try to explain that often the tissue has already been taken, and so it simply matters to just wait for the result of that test. Sometimes there may be an additional blood draw, if we are doing a liquid biopsy. There are always questions about reimbursement, about implications for family, and we have a multidisciplinary team that is really equipped to answer those questions.

Dr Felip: We have the testing, and then we have the results. How do you present these test results to patients? How are you discussing with them? What confusing points do you perceive?

Dr Liu: Well, if we think of NGS, I think the results can often be very confusing. We are often presented with a very dense sheet of biomarkers and terms that patients may not be too familiar with. So while I do give a copy of the results to the patient, if that is all we did, I think that is not an appropriate way to discuss the results, I really sit down and circle the ones that are relevant, highlighting the ones that are going to guide therapy today, so that patients understand they did have the proper biomarker testing, biomarkers that they may have heard of were looked for, and that these are the ones that were or were not found. I really mark up that sheet and make sure patients understand which ones of those are relevant.

Dr Felip: First is testing and then we discuss treatment options. After the results of this testing discussion, how is this process? You have the results, and perhaps this patient has a HER2 mutation. How does this discussion go?

Dr Liu: Well, in the United States, there is often a lot of interest in newer treatments like immunotherapy. Immunotherapy has really seized the narrative for the treatment of lung cancer, rightfully so, as it is a very important modality of therapy. When patients come in, they want to begin treatment right away. Often, symptoms will have preceded diagnosis by some time. By the time a patient comes to see me and we have these results, it has already been quite some time. Patients really want to get going with therapy. I encourage patients to wait for the full results so we can be sure to get the right treatment. We are not looking for the fastest therapy, we are looking for the best therapy, and in cases where we need to wait, it is important to do so. Once we have that information, we can use that to guide treatment. It is not denying someone immunotherapy, it is simply explaining that for this type of lung cancer, immunotherapy may not be the best treatment. Enriqueta, for you, what are some of the chief concerns that your patients have with metastatic NSCLC as they are starting therapy?

Dr Felip: I think concerns for the patients are the treatment duration, if they are going to respond or not, and also the toxicity. It is important also for the patients to discuss potential treatment options and disease progression. Also we need to discuss quality of life and symptom management. I think it is important to have a team and to ensure that quality of life and the symptoms of the patient will be controlled at the time.

Dr Liu: In the US, there is a lot of concern about chemotherapy, and I think that a lot of patients have a picture of what chemotherapy is, maybe based on television or on movies. There are certainly concerns with immunotherapy, with oral therapies. What points do you make to try to reassure patients who have those concerns?

Dr Felip: I think information is key. We need time to discuss with the patient the results of the clinical trials, to discuss the potential treatment options, to discuss the limitation of immunotherapy, and also the possibility of clinical trials. I know that, for the patient, sometimes chemotherapy is a treatment that is not optimal, but chemotherapy has activity in some of these situations. So I think information is key. Also working as a team. We have the nurses, they have a very important role in all the team.

Thank you, Dr Liu, thank you for joining me and thank you for participating in this activity. Please go on to answer the question that follows.

Chapter 6

Dr Liu: Hello, my name is Stephen Liu, and I'm from Georgetown University in Washington, DC. I'm here today with Dr Fred Hirsch from Mount Sinai Icahn School of Medicine. Here we will talk about collaborating with members of the multidisciplinary team in the management of patients with HER2-mutated metastatic NSCLC.

It really is critical to ensure that as much information as possible is gleaned from the specimen. These specimens are extremely valuable and increasingly, as we are asking more of our pathologists, as there are more relevant biomarkers, tissue preservation emerges as a critically important feature to consider when managing tissue, and stewardship of that tissue is essential to ensure proper care for every patient with advanced lung cancer. When we think about timing of testing, historically we have done this at the time of diagnosis, though in the past, many had waited until disease progression. Fred, let me ask you a question, what strategies are in place in your institution to help facilitate open lines of communication and when to do testing, what testing to do?

Dr Hirsch: Routinely we are doing testing at the time of diagnosis. We are an academic center, so we do reflex testing on most cases. That may vary from the community-based setting to the academic setting, and there are guidelines, which categories should be tested and which categories we can ease on. But in my institution we do reflex testing on most cases. We do it at the time of diagnosis, and the communication, of course, in the multidisciplinary team is important. So, tissue is the issue that has followed me for many years and it is still an issue because we need sufficient tissue for testing, right? That can often be an issue for communication. How can we improve that? How can we do that sufficiently in each case? Some of the clinical trials had a special requirement for tissue, which also needs to be addressed in a multidisciplinary tumor board.

Dr Liu: I think that we agree with that approach that it really should be done at diagnosis, and where I think some have not changed practice yet is in the use of testing for early stage lung cancer. Certainly for stage IV lung cancer our guidelines are very clear that all patients with advanced metastatic lung cancer should have biomarker testing up front to guide initial therapy. Now with the emerging perioperative data with adjuvant data, it becomes increasingly important to do these tests in the earlier stages. Is that the platform your institution has taken?

Dr Hirsch: Yes, it is. We are doing that more or less routinely, as I said, also in early stage disease, but previously it was mainly for academic reasons. Today, as you alluded to, it has therapeutic relevance with the new data.

When we talk about sparse tissue, liquid biopsy is certainly, very quickly coming into the scenario. We are moving in the direction, not consistently yet in our institution, but we are moving in a direction of parallel testing between tissue and liquid specimens. We know that the liquid biopsy does not have the same sensitivity as tissue. Meaning if you are negative on liquid biopsy, you cannot be sure that the tissue is negative. But there are also some rare cases where you have the opposite finding, where you find more in the liquid than you do in tissue. We have strong advocates for moving in the direction of parallel testing, but that is not standard of care all over of course.

Now you were asking, what about testing at time of progression? We are making attempts to get tissue at time of progression, but that is much more challenging. Here I think liquid biopsy might be even more relevant. It is easy for the patient, turnaround time is shorter than tissue, and it gives us valuable information in many cases.

Dr Liu, what strategies are in place in your institution to facilitate this communication? I think you said you have tumor boards as well, right?

Dr Liu: We do. When I think of the information that I want to get and how I communicate with the pathologist, it is very important that the pathologist is an equal member of the multidisciplinary team. It really avoids a lot of heartache in the future when we think of the role of the pathologist in helping us establish the diagnosis. Diagnosis is not simply lung cancer or non-small cell lung cancer, now the diagnosis goes down to genomics. I think the more information you provide to the pathologist, the more happy you are going to be with the information you receive, and so we tell them exactly what we are looking for.

There are cases at progression where maybe I do not want programmed death-ligand 1 (PD-L1) expression, instead we are really focused on the genomics and on the NGS. Other cases like neoadjuvant perhaps, where we want quick results, where speed really is of the essence, we will take perhaps a less sensitive test such as polymerase chain reaction (PCR) or IHC if it means getting those results a little quicker. It really comes down to communicating with your pathologist. It is just a phone call, they also have phones. You are really telling them, "What's the purpose of this test? What information do we need? And what's the priority?" Is it casting a broad net, sensitivity, or is it speed in certain cases, or are you looking for something very specific? I think the more information you provide the pathologist, the better the outcomes will be.

Dr Hirsch: Yes, I totally agree with you. Of course, the patient's most optimal therapy is in the center of this discussion. I would like to say that the educational component is good for everyone, and particularly for younger investigators sitting in the tumor boards, learning from the pathologist, learning from the pulmonologist, learning from each other. To have that communication, that is a good educational aspect to it. Everything should be focused on the patient's best treatment of course.

Dr Liu, who are the members who make up your multidisciplinary team? And you mentioned you communicate personally, you use your phone. Do you have one pathologist, one pulmonologist, or how does it work in your institution?

Dr Liu: We do not have enough of everybody, we certainly would love more, but we do have a dedicated thoracic pathologist, and we have a team of pathologists that help to cover when people are out of town or traveling, for example. In addition to the pathologist, we have an interventional pulmonologist, thoracic surgeon, radiation oncologist. Increasingly we really want the multidisciplinary team to include other members as well, palliative care, social work, dieticians, really all aspects of patient care. These tumor boards I think are very important. When you think of your institution, what role do you think the tumor boards have in facilitating collaboration?

Dr Hirsch: It has a very significant role. Another thing which I would like to mention is, I do believe there is a gap between academic institutions and the community based institutions in some ways. And we are fortunate in our healthcare system to have highly academic part of it, and we have also community-based parts of our health system. What I am trying to do these days is to bring in doctors from our community-based system to attend to our tumor boards, and we have also tumor boards placed in the community setting. As a matter of fact, for medical oncology we have 2 tumor boards, one in the highly academic setting and one in the community setting as well. I think it is important to fill in the gap between the academic setting and the community-based setting. Going back to the US Oncology Survey around molecular testing, fewer than 50% had more than 5 genes tested. That tells me there is a gap in our education towards the community. So bringing the communities into this communication is very important, and I guess your institution as well as my institution are well-suited because we have the 2 components under the same health system.

Dr Liu: Yes. Well, thank you Fred for joining me. And thank you, the audience, for participating in the activity. Now, please go on to answer the question that follows.

This transcript has been edited for style and clarity.

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